Study of pure and conjugated culture batch fermentation of Cephalosporium acremonium

Penicillin N and cephalosporin C (CPC) were produced sequentially by ATCC 36225 (69). Cell-free extracts of its mutant, ATCC 52518, catalyzed the conversion of penicillin N into cephalosporin C (38). It was postulated that the yield of CPC production might be altered when these two cultures were grown together.

Optimum experimental conditions were determined by examining the effect of aeration, agitation, and other parameters on growth. The effect of sample size on the analysis of cell dry weight was also examined to reduce experimental error. The proper air flow rate was found to be 50 ml/min in a 2-L glass fermenter when no antifoam agent was added. Microbial films were severely reduced when 60-70% of fermenter volume was used as working volume.

The relationship between the two microorganisms was found to be neutralistic when the cellular growth of conjugated cultures (ATCC 36225 + ATCC 52518) was compared with that of each pure culture (Figure 4.14). The growth yield of ATCC 36225 was twice that of ATCC 52518 and the growth yield of conjugated cultures was the same as that of ATCC 36225 (Table 4.5).

The CPC production yield of conjugated cultures, however, was less than that of the ATCC 36225 culture. On the basis of these results, it was concluded that precursor amino acids (L-(a)-aminoadipate, L-cysteine, and L-valine) produced by ATCC 52518 could not stimulate CPC synthesizing enzymes of ATCC 36225 to synthesize 3-lactam antibiotics in the conjugated cultures.